Within various chemical and pharmaceutical processes it is necessary to exactly determine a quantitative property of a certain amount of substance, for example the weight or the mass thereof. This is, for example, of particular importance in the course of the automatic filling of pharmaceutical agents into appropriate containers because it is mandatory that the amount of substance filled be exact.
Certain pharmaceutical agents that are intended to be used for a medical injection are, for example, filled into vials as powders. When doing so, the amount of powder fills only a portion of the vial. The vials are closed by means of a lid being made of metal or of a hard plastic material. The lid has a central opening being closed by an elastic seal. Immediately prior to using the agent, the medical doctor draws an appropriate solvent into a syringe, pierces the seal by means of the syringe needle and injects the solvent into the free volume of the vial. By vigorously agitating the vial, the agent powder is dissolved in the solvent. The solution which is thus prepared, is then again drawn into the syringe and may be injected into a patient. It goes without saying that during the filling process within the premises of a pharmaceutical production plant, the amount of the agent contained within the vial must be metered exactly.
Within a filling installation, pharmaceuticals are produced in large quantities, typically with filling rates of several hundred units per minute.
A thorough weight control may not be effected under these circumstances by conventional balances. One has, therefore, only been able in the past to take random samples and to check same by proper weighing, for example by weighing each hundredth packing unit. However, this procedure more and more has been considered insufficient. Therefore, the pharmaceutical industry works on appropriate standards (so-called “PAT-Initiative”), which set standards for certain pharmaceuticals, for example the above-explained injection pharmaceuticals, by making mandatory a weight control of each individual packing unit.
U.S. Pat No. 6,759,601 discloses a check weighing apparatus and method in which the weight of a filled amount of a substance may be determined in a contactless manner. Such apparatuses are identified in the art as “NCCW” (non contact check weigher). In such installations, the samples are conveyed on a conveyor belt into the area of a measuring station.
The measuring station contains a nuclear magnetic resonance (NMR) measuring installation. The installation consists of at least one high frequency coil and an iron magnet system having its magnetic poles arranged on both sides of the conveyor belt. The samples run on the moving conveyor belt through the high frequency magnetic field generated by the high frequency coil. The magnet system generates a constant magnetic field of high homogeneity at the position where the samples run therethrough, the constant magnetic field having a direction being transverse with regard to the conveying direction of the conveyor belt. The high frequency magnetic field generated by the high frequency coil extends perpendicular thereto.
By properly tuning the field strength of the constant magnetic field to the frequency of the high frequency magnetic field, nuclear magnetic resonance (NMR) is excited within the sample substance. The resonance signals are received by the high frequency coil and are fed to an appropriate evaluation unit. The nuclear magnetic resonance signal is a measure for the quantity of sample substance. By comparing with a nuclear resonance signal of a calibration sample of known weight and consisting of the same substance, the weight of the sample substance to be measured may be determined.
However, during the measuring of the magnetic resonance, the solid state material used for making the lid or the seal of the sample container, may give rise to spurious signals. If, for example, rubber or plastic materials are used, then the hydrogen atoms thereof give rise to NMR signals which may render inaccurate the measuring result as such.
In some embodiments of the apparatus disclosed in U.S. Pat. No. 6,759,601, cf. FIGS. 1, 7 and 8, the probe head configured as a high frequency solenoid coil surrounds the entirety of sample substance and sample container. These embodiments, therefore, are only adapted to be used for the measurement of liquid sample substances because it is the entirety of sample substance and sample container that is exposed to the high frequency magnetic field. Spurious signals emanating from the sample container, in particular from the lid, will not become apparent in this situation if the high frequency pulses used for the measurement are only adapted to the long relaxation times of liquids. The relaxation times of solids, in contrast, are essentially shorter, so that these solids do not contribute any spurious signals when such high frequency pulses are used. However, such long relaxation times require that the samples that are fed to the apparatus at high velocity, be magnetically biased prior to reaching the high frequency coil. For that purpose the prior art apparatus has a magnet system being configured so large that the constant magnetic field is already effective in an area upstream of the high frequency coil.
On the other hand, there is a substantial need for installations, for example NCCW installations, which are likewise capable of measuring quantitative properties of solid sample substances, for example for measuring the weight of the injection pharmaceuticals discussed at the outset.
Further embodiments of the apparatus disclosed in U.S. Pat. No. 6,759,601, cf. FIG. 9, therefore, are adapted to excite magnetic resonance only within a portion of the sample container in which the sample substance is contained. By doing so, the excitation of spurious signals from the lid or from the seal shall be avoided. For that purpose, according to a first alternative, gradient coils are arranged within the measuring station, in order to superimpose magnetic field gradients on the constant magnetic field, thus permitting a local excitation of magnetic resonance. According to a second alternative, high frequency solenoid coils are arranged within the measuring station below the conveyor belt, so that they are arranged closer to the sample substance as compared to the lid or to the seal, resp.
The afore-mentioned first alternative has the disadvantage that the structural complexity of the installation is greatly increased by the need of providing an additional gradient system together with an appropriate supply and signal evaluation. The operation of the installation becomes likewise more complicated.
The second alternative, first, has the principal disadvantage that the excitation of spurious signals from the lid or from the seal, resp., may be reduced only slightly because the sample substance is located in the direct vicinity of the lid and of the sealing, resp., in particular when the probe container is fully filled with sample substance. In such a situation, the high frequency magnetic field being generated by a solenoid coil arranged below the conveyor belt and being directed upwardly, reaches the lid or the seal, resp., at almost unreduced amplitude. Another disadvantage consists in the fact that a high frequency magnetic field being irradiated from below at a distance is significantly less homogeneous as compared to a field that is generated, for example, by a solenoid coil surrounding the sample. This may lead to errors in the measuring result. Finally, the magnetic field must be irradiated at a high intensity. All these problems become more important, the bigger the distance is between the high frequency coil and the sample substance. Moreover, this second alternative requires separate structural units, one above and one below the conveyor belt.